Baylor College of Medicine

The Neuroscience of Losing Touch with Reality and the Mysterious Hierarchy of Sensation




[Intro Melody]

Juan Carlos: And welcome back to the Baylor College of Medicine Resonance podcast. I am your president and one of your hosts Juan Carlos Ramirez, and in today's conversation, we will be interviewing Dr. Jeff Yau. Dr. Jeff Yau earned his bachelor's from the University of North Carolina at Chapel Hill in Psychology and then he went on to get a Ph.D. in Neuroscience from the University of Johns Hopkins.

Juan Carlos: Dr. Jeffrey Min-In Yau's lab is particularly interested in Human Psychophysics and his lab aims to identify perceptual and neural processing principles that unify our senses and to characterize the complex interactions between the sensory systems. The lab is also interested in understanding how human brain regions collaborate in distributed networks and how network connectivity is dynamically modulated across tasks and attention States. The lab investigates the relationship between the brain and behavior using functional neuroimaging, non-invasive brain stimulation, computational modeling, and psychophysics.

Juan Carlos: In our conversation with Dr. Yau, we'll learn all about his lab, what he does, his journey, how he got there and what drives him, what drives his curiosity to know more about how the brain integrates these different sensory modalities under varying states and locally, Dr. Yau is known as an amazing mentor and is embedded deeply in the QCB and Neuroscience programs here at Baylor College of Medicine. Let's go to the episode.

[Interlude Melody]

Kiara: I'm so happy that you agreed to do this. Thank you so much for agreeing. I'm Kiara Vega. I'm a fourth-year neuroscience student in the Daoyun Ji lab and I just want to start by asking you to tell us a little bit about your academic trajectory and research background like how you got here.

Dr. Yau: Right? So, I will start by saying, thank you very much for having me, and this is really a pleasure for me. So, with my background, I started as a Psychology major when I attended University of North Carolina Chapel Hill. And initially when I started, I was really interested in sort of, psychology. I was thinking about going to medical school for Psychiatry and then just sort of as an undergrad, through various research experiences, I ultimately realized I didn't want to go to medical school and that research was sort of the more interesting bit and we could get into the details later. But then after undergrad, I then attended Johns Hopkins University for my Ph.D., I got a Ph.D. in neuroscience and then finish there. And then completed a postdoc in neurology at Hopkins. And then I moved to Baylor and started my own lab in 2014.

Kiara: Um, what type of research did you conduct when you were at Johns Hopkins and doing your Ph.D.?

Dr. Yau: Right. So, for my Ph.D., I worked on the neurophysiology of somatosensory processing and so we were working with non-human primates and recording from electrical signals and somatosensory cortex as we were presenting basically, sort of, cookie-cutter patterns to a monkey's hand. And then we were characterizing how our somatosensory cortical neurons selected for the spatial patterns that they were experiencing on their skin.

Kiara: Oh! So, you were always interested or were, have been working with somatosensory processing for a while now. Yeah?

Dr. Yau: Yeah. So, even as an undergrad I was working in a somatosensory lab and so, in many ways, my undergraduate experience has shaped my research trajectory. And, and I can even say, my first RO1 was based on a research idea that came about as a question that emerged when I was doing research as an undergrad.

Kiara: Why was that what drew you in to neuroscience, like…?

Dr. Yau: right, so I would say that my experience with research is probably typical to many people that I know where there's sort of a series of chance events and serendipity that sort of brings me to where I am, right? And so, as an undergrad, I had worked in a number of different research Labs. I was, I started in a Pathology Lab where I was working on cancer biology, angiogenesis, and prostate tumors. And then in parallel I was working in the social psychology lab work and how people make decisions about social interactions. And then it was in my junior year of undergrad that I took a Sensation and Perception course, and at the end of this, the graduate TA, Sliman Bensmaia, who was teaching that then said, "hey, you know, you're pretty bright. Do you want to come in work our lab?" So, then I said, "cool, let's do it." And so, then I joined Mark Collins lab working with Sliman, and their lab was looking at somatosensory perception. So, "how do you perceive vibrations?" And, and then that sort of set me off, ultimately, on the path that I am at now.

Kiara: Yeah. Wow, it's pretty interesting.

Erik: Yeah. Yeah, and I was, I was, we were talking a little bit before but for anybody any of the students listening, now or prospective students listening, Dr. Yau – at least taught, I'm not sure if you're still teaching the medical students.

Dr. Yau: Yes. Yep!

Erik: the neurology course, or the neuro course, learning about all the tracts and, and just we were talking about how you, you kind of liked to show, you know, how everything kind of lined up, you used was a TMS is what it's called, right?

Dr. Yau: That's right. So, Transcranial Magnetic Stimulation.

Erik: Yes, and I mean, you know, they use it in more sophisticated way now throughout neurology now, but it was definitely very cool to see you, would just stimulate your hand to move by, you know, just a volt. Yeah. It was very interesting.

Kiara: Yeah. Yeah, and he [Dr. Yau] also is a director of Neural Systems class course in Neuroscience. Yeah. I wonder how you did you volunteer for that? Because I know people, right?

Dr. Yau: So, I indicated that, that I would be interested in teaching and I think through a few years of teaching, guest lecturing, I think then. But ultimately, I indicated that was interested in teaching. I think I've demonstrated some competence at it and then I was essentially assigned to be a course director.

Kiara: Yeah. It was a really, your course lectures were really exciting. So…

Dr. Yau: Great. Thanks.

Kiara: I do think it was good. So, actually, I want to know how does one study multi-sensory processing and perception? Especially tactile information processing?

Dr. Yau: Right. So, I think, I'll maybe answer those questions sort of, in reverse order. Right? So I think that in general, the way that my lab thinks about studying perception, and for touch in particular, is we want to first be able to systematically and quantitatively characterize the way that you experience sensory inputs, right? And so, for touch, then we're delivering mechanical stimulation to the skin through very well-controlled motors that can deliver, vibrations, or indentations to the skin and then we design what are very simple, but I think elegant and, and I think well-controlled behavioral experiments in order to measure how people experience those patterns that we delivered to their skin. So, then we call this psychophysics where we're measuring their perception of this information.

Dr. Yau: Once we characterize the way that they are able to perceive and discriminate sensory inputs. Then the goal is to say, how does the nervous system support this? So, then we go and measure brain activity in different scales with different tools and then ultimately try to find a correlate to the perceptual patterns that we saw, right? So, I think just taking sound perception as a very simple example that everyone can sort of follow you. One could hear two tones "boop-boop" and then you ask them which one of those sounded like it was higher in frequency, and then we can just repeat that process, many, many, many times as we manipulate the parameters of those sounds and then through this experiment that we can characterize, how sensitive someone is to frequency differences in the sounds, what is their bias in terms of how they perceive individual frequencies? And so, we do that with sounds, we do that with touch in terms of vibrations, and then that's how we then sort of create a profile for how individuals perceive sensory inputs.

Kiara: Nice!

Erik: Well, and can I ask maybe the question that maybe some neuroscientists or non-neuroscientists rather, might be thinking because you know, I don't have any experience in wet lab Neuroscience. Are you studying, the -- how are you studying the brain? It sounds like you're basically studying the connections between neurons. Yeah, you're using fluorescent microscopy to look at kind of the neural connections in the brain or what do, what are you doing?

Dr. Yau: So, up to this point in the six-plus years I've had my lab here at Baylor, we've been using purely non-invasive methods.

Erik: Okay.

Dr. Yau: …you characterize responses in the human cortex, and so, then this includes fMRI -- functional magnetic resonance imaging, and so that we're measuring essentially, a blood flow correlative of brain activity, but as I mentioned to you earlier, the lab is moving in a direction where we want to get a more mechanistic understanding of sensory representations, and so then this is where we're moving into more animal model systems using more invasive. E-phys methods.

Erik: Okay, "E-phys" standing for electrical physiology, I guess. Yeah.

Kiara: Sorry!

Erik: No. No, it's all good. I could make sure I'm…

Kiara: Actually, that reminds me that I was wondering, um, so, you know, that humans rely mostly on vision, right? To perceive the world is—

Dr. Yau: That's debatable. But okay.

Kiara: Now that's exactly! That's the, that's my point. I wanted to ask an expert if there's really truly a hierarchy to the senses.

Dr. Yau: Yeah, right. So, I think that's a great question and when I teach the medical students, one of the, what-- if I remember during my lectures--I often say, "if you have to sacrifice one of your senses, what would you sacrifice," right? And so, would you give up your sense of sight, of hearing, touch, smell, taste, right? And Covid times, right? Losing sense of smell and taste that people can clearly get by with that. And I think what's interesting is most of us intuitively have an idea of what does it mean to lose your sense of sight. What does it mean to lose your sense of hearing? But really no one has an idea of what it means to not have your sense of touch. And so, it turns out that touch is really, really important, not only for you to sense and perceive your environment, but in fact, in terms of guiding how you would/can interact with your environment, right? So, your motor system, if you don't have a sense of touch, is going to be really, really, impoverished and you're going to have a hard time having highly coordinated actions and you can't reach out to touch things. You can't reach out to move and manipulate things without a sense of touch.

Kiara: And, and also like, you can harm yourself more easily, you know, like if you can't feel that your hand is burning or some like that. I remember everything. I'm so sorry. If we're a little tangent, you might edit this out, but I remember a house episode were this woman, she couldn't feel, she didn't have the sense of, like, tactile perception.

Dr. Yau: Right.

Kiara: Yeah. So yeah, and that's when, when I started thinking, you know how important it is. So…

Dr. Yau: Yes, for sure.

Erik: So that being said, it sounds like, Dr. Yau, would you say if you had to lose, if you couldn't lose one? You would. You want to keep I guess, proprioception goes into that, and right?

Dr. Yau: Yeah. So, when I say touch, I would say proprioception is one sort of sub-modalities of touch, although I think people would argue that, right? So, proprioception is how you perceive where your limbs are in space, right? And, but I think just cutaneous signals of the stuff that you get from your skin, that's also, you know, really intimately tied to perception, and all of that is guiding the way that you can perceive where your limbs are and also how you're interacting with things of the world. So, how well how much force you even applied to pick up an object, right? All of that is really finely tuned so that you're not just crushing it every single time because, you know, this is just the right amount of force that you need to apply. And…

Erik: Yeah, I feel like if anything robotics may have made people appreciate that more people getting into trying to, you know, emulate the hand. It's robotics. It's like realizing how much circuitry and logic is required to just do that. All right, route. Yeah. Yeah.

Dr. Yau: And so, I think to your question then of, you know, is there a hierarchy? In terms of what sensory modalities are important, I would say that it's, I wouldn't characterize it that way, right? Because I think in the end it's sort of an apples and oranges like each different sensory modality is providing you information that is specific to what the receptors are able to signal and, and so, then you will rely on some senses for some behaviors more than other senses. And, and I think what's also important, and this gets to the question of "Why do I study multi- sensory processing?" The different sensory modalities can convey redundant information, right? So, what you see about spatial information is also conveyed by your sense of touch when you touch something, right? So, I can know that this is a mug because I could see it but I can also hold it with my hand and know the shape of that, right? And similarly, what you hear, gives you temporal information in the same way that when you feel vibrations in your environment that's giving you the same temporal information. So, I think the nervous system and the really compelling questions for me are "How does the nervous system combine these redundant sensory cues over the different sensory modalities?"

Kiara: Wow, that's really interesting. It's also interesting to see how, I mean, I wonder for me, now, just thinking about these things…how humans develop this, you know, like a kid, a baby, how they develop, you know, they fine-tune their perception in order to,um, to actually be able to manipulate them, um, but something I wanted to ask you was what are the clinical applications of this research? What are you—

Dr. Yau: Right. So, I think that for us, if we think about understanding the neural basis, for how you sense and understand information in the environment then allows us to have potentially a grasp on what we can do when that ability is dysfunctional or repaired, right? And so, if we know that for example, parts of the brain are supporting both hearing and touch together, right? That we might be able to leverage that information when there were developing interventions for treating deafness, right? Or one of the ideas that we've thought about, in other labs, have also considered this as with cochlear implant patients, right? So, they've received this cochlear implant. They're stimulating the hair cells where the auditory nerves in order to drive this signal, but if they've never experienced these peripheral signals from the auditory system, then the brain might not actually really understand how to interpret that as sound, right? But if that part of the brain is/has been processing frequency information by touch your whole life, then we've thought about this as, maybe you can think of this as tactile training wheels, right? So, you pair sounds with vibrations of a particular frequency that are matched and now the brain is saying "Oh, yeah. I know that that's a 200 Hz signal." So, when you receive this cochlear input, now they can match that as sort of strengthen that connection centrally and so and, you know, I think the evidence still remains to be shown that that is, that type of plasticity is happening. But, clearly recent in just the last couple of years before showing that cochlear implant recipients benefit in trying to understand speech in noisy environments when they also experience correlated vibrations that can be delivered to the wrists, so that's one way to think about this. Just from the tactile domain alone. If we understand the neural basis for how sensory information is represented in cortex, or even in the afferent nerves, then, potentially you can develop bioengineering approaches or neuroprosthetics where now you can deliver artificial touch, right? So, you can stimulate the nerve or cortex directly and now you can bring the sensory input for people who have, let's say, imputations or people who suffered spinal injuries and they're quadriplegics, that they can't get signals through their peripheral nervous system.

Kiara: Speaking of that. Can you speak a little bit more about the neurological basis of phantom? Limb? What is going on there?

Dr. Yau: Right. So, Phantom Limb experiences are experiences of amputees or people who suffer from limb loss and despite not having that limb, they still perceive the experience of that, right? So, this could be benign sensations, or this could be in the form of pain and the current knowledge is basically that you have representations of this limb that are preserved in cortex, right? And so, just as sort of jumping back to more of a background, sensory motor cortex contains very systematic mapping of different parts of the body onto different populations and circuits in the brain. And so, this is typical. And so, you have a body map in your brain through the sensory motor homunculus. One of the long-standing questions has been. Well, what if you lose your limb? Now what happens to that body map? And for many, many years, people thought that, that body map would then sort of change and adapt, and that those neural circuits that are repurposed to represent other limbs that are still there. With amputees, now there is more and more evidence that the map actually doesn't change so much. And so that once you had this initial patterning of them back and you have some representation of your hand, for example, even after you lose your hand, your brain is still representing the hand, that's there, right? And so, then when you have electrical activity or neural activity in that cortical representation of the hand, that's still then is inducing the perception of that hand being there and doing stuff.

Kiara: And…

Dr. Yau: So, let's, go ahead.

Kiara: I'm so sorry. I just wanted to know if this syndrome, does every amputee experience it? Experience it?

Dr. Yau: So, in the, I would say that phantom experiences are very, very, common and I don't want to go so far as to say every single amputee experiences them, but they are definitely very, very common. We've worked with populations of individuals who suffer from lower limb loss and with every single participant that we've recruited a tested interviewed, they've reported that they've experienced phantom sensations at some point. That experience evolves and changes over time and so immediately after limb loss, that could be a much more acute and severe experience and gradually over time, that could be attenuated or sort of the quality of that can change. But you know, I would say that it's definitely a very common experience. I think what's more variable and I guess one thing that was interesting for us as we were doing this study was realizing just how different everyone's experience of phantom sensations and sort of phantom pain could be and there really wasn't a very standard experience or a sort of homogeneous pattern of what our participants were reporting and even in terms of the type of experiences that they have for their phantoms could be different, some reported tickling sensations on their phantom limb. Others reported feeling as though their phantoms were moving, right? And others just would report that there are, sort of, waves of sensations almost like air. That's being brushed up and down along their phantom limb. Now again, the amazing thing is they don't have a limb and they're still feeling it as though it's on their skin, right?

Kiara: And, do they feel pain?

Dr. Yau: So again, it varied, so some of our participants reported pain that was, that could be very severe at times. Often times they would be treated and therefore pharmacological interventions to try to deal with the pain. But then in many cases our participants also reported that they initially felt phantom pain, but then that would go away or that would suddenly emerge, you know, abruptly and acutely without really a clear thing that would trigger that. So, I think that again there's a that we don't know about this.

Erik: Yeah, if I could just ask a question, so well, and so as if I can ask a question on the back of you saying, we don't know a lot about this. Um, it must it sounds like, it must be an issue with the peripheral like, you know, you've got it. Everybody's experience is different because everybody is peripheral nerves, like, sensory nerves. That are maybe torn or going to be torn in a different pattern. You know what I mean? Like, is that kind of what the thought is, is like this person just has maybe a more sensitive whatever, pacinian corpuscle or whatever. The stuff are, you know? Yeah. Merkel cell.

Dr. Yau: Right.

Erik: Well, the peripheral nerves. Is that true though? Is that kind of what the thinking is?

Dr. Yau: Yeah. So, I think that that certainly is going to be part of it, right? But I think that, in addition to the variability that you see, in whatever the state of the peripheral somatosensory system is, I think cortical changes and the variability that you see in cortex is also going to matter, right? And I think that with the certainly with upper limb amputees, right? So [researchers] at USeattle, they've done a series of studies, over the last nearly decade now, showing that with upper limb amputees, cortex in some cases can remap and that remapping will then depend on how you use your residual limb. So, the part of your limb that is the remaining. For participants, amputees, who don't use their limb at all versus participants who then try to use their residual limb in different ways, right? That, sort of, the functional use of your body can still drive some degree of remapping in cortex. And therefore, the representations of the missing limbs can still be malleable to some degree.

Erik: So then the pharma-- it sounds like in the pharmacology to treat this must not just be a peripheral like lidocaine or something.

Dr. Yau: That's right.

Erik: Maybe an opiate that, that it's going to work on the sensory. What is it? The thalamus? That takes the pain?

Dr. Yau: Yeah. So, I think with pain, right? I would say that with painful experiences of your phantom versus benign experiences of your phantom, there could be very different neural systems that maybe are overlapping but also doing independent things. And so, the pain is definitely potentially just tapping straight into the neuromodulatory system related to nociception in pain and not really even dealing with the phantom representations per se, right?

Erik: Right.

Dr. Yau: Yeah. So, I think that, that's sort of a much more complex thing, as well, right? Like, yeah, and again, like if you have if you're experiencing pain of a headache, right? When you treat that with some medicines, it's not like you're treating the underlying cause of why you have that pain. You're actually just dealing with the signals that are, you know, creating that percept of the pain.

Erik: Okay. Thank you. Not to belabor--I won't belabor it. Thank you.

Dr. Yau: Oh no.

Kiara: Yeah, that's exactly. That was exactly my question about, like, having nociception.

Dr. Yau: Yeah, let me add one other thing because this is kind of a cool result that would Tamara's group and then what we've also been doing the lower limb amputees. I think its sort of worth noting, right? So, a lot of people can experience phantoms just spontaneously, just sitting there, right? But the other thing that has been more revealing is the fact that people can voluntarily control their phantoms. And so, in our studies to characterize, what part of the brain is still responsive to a phantom. What we've done is we've asked our participants as we're scanning their brain using MRI, functional-MRI. We say during this period of time, just move your phantom, roll your phantom foot and, and, then for, they vary on how salient this experience is for them. But you know in nearly every one of our participants when we sort of explain to them. "Yes. I understand you don't have a foot anymore. But assuming that you did think about moving it. Not just imagine seeing it move but actually move it. The way you would your sound foot," right? And when they do that, that's what we see that the part of the brain that normally would represent an ankle or a lower limb becomes active in this MRI scan, because during the time that they're moving their phantom limb.

Dr. Yau: And so, that again this is sort of revealing that those circuits are still there. Right? So, we've tested people who lost their limb 40 years ago and yet despite that passage of time when we say, "Hey, you know, if you can feel your phantom, try to move it and they can deliberately voluntarily move that. Then we see activity in that part of the brain that's responsible there.

Kiara: Without any proprioceptive input, right?

Dr. Yau: Yeah.

Kiara: That's really interesting. So, okay, so I want to move on and address some of the aims of your lab, which purportedly aims to identify perceptual and neural processing principles that unify our senses and to characterize the complex interactions between the sensory systems. My question is, have you been able to identify any such principles and if so, which?

Dr. Yau: Right. So, uh…

Erik: We ask the hard questions here.

Dr. Yau: That's right. Yeah, that's right. You're not you're not pulling your punches here. So, I would say, you know, this actually goes back to some of my work from earlier in my career, even going back to graduate school as well, where you know, I mentioned earlier in our conversation that the different sensory modalities can convey similar or even redundant information, right? And so, one of the things that we've been interested in is understanding what is the type of information that can be similarly redundantly signaled. So, for example, I'll give the example, the example that in vision you can see spatial information about object shapes, right? And but by touch, you also have spatial information that you can perceive with the orientation of things that you experienced on your hand, the curvature of those. So even for my Ph.D. work, what we showed was that the ways that visual cortex neurons encode spatial information is analogous to the way that somatosensory cortex neurons encode spatial information. So, they're sort of common neural codes. The way that information is represented on neural levels can use sort of analogous formats, right? And so that makes sense, right? Because ultimately, if the brain wants to combine that information that you want those different neural populations to be signaling that information using the same language. And so, then from vision and touch, we can think about spatial correspondences in sensory processing. And then with, let's say audition and touch, again, these are two different modalities that are sensitive to mechanical oscillations or environmental oscillations, right? So, sound waves and then also mechanical waves that you feel through your skin, so we spent many years understanding how the two sensory modalities interact in terms of frequency perception. So, if you have people feeling vibrations, "Bizz—Bizz" and you have them judge which one of these was higher in frequency. They can do that. Even if they don't hear any sounds. But we've also shown is, if at the same time, they're doing that, they hear a sound "Dooop," that sound will systematically bias the way that they experience those vibrations, right? And so, then what we now are starting to look in the brain and say, "what are the brain areas that are active to vibration stimulation or to sounds?" That we see that there are some regions that are, that are commonly active and then ultimately, the idea is, to go into those regions and say "at a neural level, what are individual neurons representing in terms of the touch, and in terms of the sounds? What are the computational principles that then explain how these neural populations are integrating this information between touch and sounds?"

Kiara: And speaking of neural, populations that integrate information. This makes me think of hippocampal place cells that are…

Dr. Yau: Yeah, that's right. They are combining information over many, many different sources, right?

Kiara: Yeah, multi-modal information processing. And that's pretty that, that would be another, I guess way to study that.

Erik: Can I ask a quick question, when you're talking about the neural code. How, what is our understanding of the neural code at the like, how, what's the depth of it? Are we understanding like it takes this, many neural connections to make an input like this or, you know, does that… Does that question, make sense?

Dr. Yau: Yes. So, that makes sense and my answer may not make that much sense. Okay, I would say that there's, we can understand neural codes at multiple levels, right? And so, I would say that there's very simple codes that we now have very clear understanding of those. So, for example, we know that in visual cortex, the way that visual cortex is organized, is retinotopic. So, that different neurons are organized in cortex according to what part of the visual field they're sensitive like that.

Erik: Yeah. Like a map?

Dr. Yau: That's right. It's a retinotopic map, right? And just like, in somatosensory cortex, mentioned before, there's a body map, so different neurons, and cortex are organized, according to what parts of skin they respond to, right? So, that's a code and we can exploit that. Because now if you go in and you stimulate those populations of neurons strategically and in a very fine way, now, you can evoke percepts that are localized to a particular region of the retinotopic space or two part of the body, right?

Erik: Then, which is what you would get with TMS, right?

Dr. Yau: That's right. And so, with TMS which is a much coarser method, right? We can at least activate, you know, muscle commands in particular muscle groups, but with finer methods where your electrically stimulating local populations of neurons, you can actually induce these artificial sensations that then you could spatially control, right? So that's one level of neural coding that we know that we can play around with. I think a little bit beyond that you can say, what features of what information are these neural populations tuned for separate from just a location in space, right? And so, then you we know that there are neurons in the visual system or the somatosensory system, that may be tuned for different bars at different orientations. And so, if you evoke activity in those, you might be able to reduce the perception of a contour, like an edge that is oriented in a certain way or curvature that's in a certain way, right? And so, then that's sort of getting at, again, some neural representation, some code of information that how that maps activity, and then you can leverage that in order to generate percepts or to manipulate percepts

Erik: So, it sounds like we're, I'm just trying to think for a coding analogy. It's like we're at the python level but we're not at the like, the, you know, machine language level of looking at, because that's what I'm saying is like what's the what's the depth? We what you're talking about is spatial representation, which I think is important but like understanding at the bit level if you will, that's when you talk about code. I was just wondering oh, yeah, you know, especially because I don't have a finger on the pulse of development or progression in this.

Dr. Yau: Yeah. Yeah. So, then I think to your, to that question, it gets more subtle and more sophisticated too, right? Because we could talk about for a given neuron, well, we say that this is sensitive or a particular type of information. What about the activity of that neuron relates to that? It's not just that information is represented in a "wamby-pamby" sort of arbitrary way, right? There is, it could be just the total numbers, right? So, it could be a rate code. It could be the particular temporal patterning of that activity that is conveying the specific information and so that I think is actually getting to coding, right? It's actually the way that that activity relates to this specific information and then you can even start talking about, you know, how much information. What are the bits of information that are contained in these neurons' activity?

Erik: Okay. So, we are getting there, that it sounds like.

Dr. Yau: Yes, and this is something that for decades, you know, neuroscientists have been working towards already.

Erik: Okay. Well, maybe they need a better PR agent, right?

[All laugh.]

Kiara: Yeah. Honestly, yeah, like for example, in our lab, you know, we study hippocampal Place cells and the way that we try to decipher a kind of the neural code is based on firing rates, right? So, yeah, like you said, there are you can study the neural code. There's just like so many levels to it.

Dr. Yau: Yeah, right. Yep.

Erik: Well, thanks for, sorry. That was a getting us on a tangent. But thank you for answering my…

Kiara: I think that's a fascinating question. Yeah. Okay. So, how would you explain synesthesia?

Dr. Yau: Right. So, synesthesia, just define it for everyone is the sort of the atypical experience of some sensory inputs that often results in sort of confusion, or at least a re-representation it as some other form of information or so, for example, you could potentially associate, you know, certain letters or colors with particular or letters or numbers like the visual form may be associated with particular colors, right? So, this is a grapheme-color synesthesia and people synesthese who experience that do that automatically and it's something that doesn't really require that they tried to do that. And one thought is that these types of experiences just reflect some atypical connectivity between again, neural circuits that are representing this information, right? So again, if you have neurons that are tuned for spatial form information in the brain, and then there's other neural populations that are tuned for color, normally these may be somewhat segregated, or at least, they're not, they don't connect and communicate with each other in a obligatory forced manner, but in individuals with synesthesia one possibility, is that these neurons now based on some type of you know, atypical connectivity are now communicating in a forced way. So, that now when you activate one population, the other one is also activated and therefore, you get this associative experience.

Kiara: That's interesting in the context of you saying, you know that different sensory pathway is they, they, convey redundant information, you know, so maybe there are some crosstalk, right?

Dr. Yau: Yeah, so that sounds right. I think that and, and, this is maybe a debatable semantic point but…

Kiara: Right.

Dr. Yau:  …in many ways you can say that the way that our nervous system normally wants to combine multi-sensory information already reflects a degree of synesthesia in everyone, right? Now, this is sort of a natural normal thing. But yet there's also ways where that gets sort of integration on steroids and that's where you have information that normally doesn't need to be combined or isn't even naturally associated, but yet, because of the way that the biology now is wired, that becomes integrated.

Kiara: Right. That's really cool. Another question that I think is interesting is how do we process sensory information when we're asleep? Is it the same as being consciously aware?

Dr. Yau: Right. So, now we are moving away from my expertise. But I mean, I think that…

Kiara[Laughs] Sorry.

Dr. Yau:  No, no, I mean, I think in some sense I would think about this as one we definitely are able to process sensory information while we're asleep, right? So that's, you know, undeniable. I think then, what then is important to consider is sort of an issue of processing that depends on awareness or processing that leads to awareness, right? So, if you play a sound while I am sleeping, there are parts of my cochlea is definitely going to represent that information signal through my auditory nerves, go through many subcortical regions, whether my auditory cortex is active to that sound, I don't know, right? But, but maybe there are parts of primary auditory cortex, that is still going to process that. But then, the higher order areas that are responsible for how you understand that information? How you make decisions about that information…

Kiara: How you perceive, right?

Dr. Yau: That's right. That's right. Those may be the ones where, you know, they're tied to conscious experience or tied to awareness. Those are the ones that maybe will not be processing that during sleep.

Kiara: Exactly. So, the way that we process sensory information might be more or less the same but then our perception is tied to our, our, brain state, you know, whether we're conscious or unconscious. So, that's kind of interesting.

Dr. Yau: Right. But we're, and I would say to that, right? I think you can maybe divide this process into sensation, which is just the signaling and encoding of this information versus perception, which is your experience, your decoding of the activity pattern into and making use of that is some sort of cognitive way, right? And so, maybe the sensing part is always there, even when you're asleep, but maybe there is still attention, is going to negate that to some degree, right? But then now you're sort of sensing part of that though or the perception part of that, right? How you understand that whether or not you're even aware of that, that may be, what is really sort of cut off when you're asleep or you know, cut off in a way that it's doing something else, right? Because again when you are sleeping, it's not that your brain shuts off, there are still spontaneously activity patterns, there is still structured activity patterns. And so, you know, whether or not you're aware of that and experience that, that's I think the challenge of understanding sleep.

Kiara: Yeah. I have this as an optional, you can answer if you know any, if you know about it or not, but what can you tell us about sensory processing? When the brain is, it is in an altered state. So, like either an extreme stress or under the influence of something?

Dr. Yau: Right. So, I think this is a very interesting question that, you know, I think philosophers have wondered for centuries and, and, and then also, I think more recently from a, you know, neuropharmacology psychiatric perspective. It's also had more of an awareness and interest, right? So, for example, the use of psilocybin and as a intervention for treating different Affective disorders or mental health disorders, I think sort of highlights the potential utility of this. And so, the limited understanding I have is that, especially if we sort of link this to sensory processing, right? Is that there may be a very clear modulatory effect of states and these chemical intervention modulators on the thalamus. And so, the thalamus is sort of this relay station where it's connecting to many, many different parts of the brain, many different sensory areas. Its providing bottom-up, sensory information, that get projected into these subcortical areas. It's receiving feedback from all these higher-order areas and primary sensory areas. And so, if so that gives this sort of the very important hub quality, right? And so now if you have some sort of neuromodulator that's influencing the activity of thalamus and the way that the hub is now relaying information, and again, integrating information or separating information…now this, you know, singular hub could potentially already explain a lot of the different experiences that you have under these altered states.

Kiara: Yeah. I had read that; I had read a long time ago that it actually increased the crosstalk between brain regions that usually wouldn't be and yeah and connection with each other. So I thought that'd be pretty interesting.

Erik: Well, in, so Dr. Yau, I guess maybe you would have just left Hopkins before they started. Were they doing the ketamine trial for depression while you were at Hopkins? Because I know that's one. Hopkins is starting to get into a lot of, right?

Dr. Yau: Yeah, so Hopkins, I think Bayview, right? They were doing a lot of these types of studies. I think during the end of my postdoc, they were starting to do some of these words with a ketamine also with psilocybin.

Erik: So yeah, so it'll, it'll, be interesting. We'll see what happens.

Kiara: Yeah, they're, I mean, so far, the results are promising. I think, and this is a bonus question. But which is your favorite sensory pathway?


Dr. Yau: Well, I think from this conversation is probably clear that I spent much more time thinking about touch than other sensory pathways, so sensory systems. But in the end, I think, you know, what's also clear, hopefully from this conversation, is that part of what I've been focused on with my own research in my own interest is not just focusing on touch, per se, as a sole, you know, model system for understanding sensation and perception. But really looking at how does touch interact with other sensory modalities, right? And so, with that then I've also tried to keep knowledgeable about the visual system in the auditory system and then understand how do these different sensory modalities relate to each other and how do they interact with each other? So, because ultimately, we can you know, maybe end on this sort of high-level thing, right? The way that we experience the world is truly a multi-sensory experience. And so, you know, if you look at sensory neuroscience, historically, people have said "let me go study one sensory modality. Let me go study one particular question" and they really drill down in this reductionist way, which I think is very, very, helpful. We've learned a lot in that way, but it really doesn't reflect the way that we normally experience the world. So, I think moving into an ecologically valid understanding of the neuroscience of perception. I think, then it kind of requires that we take into account. What is happening normally? What are the natural statistics in our environment and multi-sensory signals is really a sort of the common the way that we experience the world. So, this is where…

Erik: By ecology, you said psychological, are you talking about…At what level of ecology are you talking about? Just sorry, I was confused by…

Dr. Yau:  Yeah, so, by ecologically valid, I mean sort of behaviorly valid in just your normal experiences.

Erik: Okay.

Dr. Yau: Right? As opposed to, again this very reductionist, lab controlled, we only do one thing in isolation from everything else.

Erik: Oh. Okay, right. Gotcha.

Dr. Yau: So, like, even as we sit here, right? Like, you hear me speaking, but then through the camera, you can see my mouth moving, right? So, there you have visual and auditory information that's correlated. And so, then it almost doesn't make sense to necessarily think about speech perception in hearing alone or speech perception from lip reading alone. It's really, you know, the natural way that we experience is information is this multi-sensory signal, right? Yeah. So, the way that we experience touch, and this is something that you can try with people at home listening. This can try, you know, if you have your hand, and you brush this over a surface, right? You'll feel the vibration. So, you understand the texture that is under your, your, finger, but you'll also hear the sound of your interactions with this surface, where you hear that each "Sch-sch-sch-sch-sch!" And so, if you brush your hand over different surfaces, you'll actually hear the quality of that sound change, right? It goes from "Scha-scha-scha-schuh"  and become lower frequency, or if it's rougher you'll hear a different type of sound. And so that also tells you that the way that we experience vibrations by touch is really correlated with the way that we experience sounds that are tied to those interactions. And again this, this sort of motivates why I'm interested in understanding how our nervous system combines sound and touch information with respect to these types of environmental cues.

Kiara: What are the brain regions where you say, you would say these multi-sensory pathways converge?

Dr. Yau: Mhm. Right. So, the traditional view, right? The, sort of, textbook view is that you have brain areas that are dedicated to different sensory modalities individually, and then you do a bunch of processing and then these higher-order areas and posterior parietal cortex and frontal cortex or sort of the juncture of parietal-temporal lobes. Those are, sort of, the higher order areas that this information is being integrated. I mean that's certainly true, right? That you have more of this convergence in those areas. But I think over the last two decades, now, it's also becoming more obvious that even these areas that are traditionally thought to be primary sensory areas that are dedicated to modality can be clearly modulated at least by other sensory modalities in very specific ways, right? So then in that sense, you can argue, and people have argued, right? Is there any part of the brain that's truly uni-sensory or is really everything, reflects some multi-sensory convergence in some way or another? And I think that then the question moving beyond where the brain is happening. But I think the more interesting and more difficult question is, what is actually happening in those areas, right? What is the information that is being combined? What are the computations that are underlying, this combinatorial process?

Kiara: Yeah, precisely. I agree and do you study these brain areas to kind of understand the computation,

Dr. Yau: Right. Yeah, so, you know, I think part of what we've been doing with, you know, the non-invasive methods, functional MRI is to try to even just identify where are the brain areas where I mean, the brain is large and he could just sort of blindly stabbed in and say, I hope that this is here, but, you know, I think using some invasive way that's at a macro scale, we can at least identify this part of the region is a candidate region where this information could be coming in. And then the goal would be to use the more invasive methods, that give us a finer scale, measurements to be able to say, you know, what is that activity? What are the neural correlates? What are the computations? But even from a behavioral side, and you know other colleagues that we have here at Baylor and other institutions have developed very rigorous quantitative frameworks for understanding perception behavior, which at least allow us to infer these are computations that the nervous system may be using or maybe implementing that support this information processing and these types of behaviors, right? So then in that sense, we already have a guess at what might circuits of the brain be doing. What are the computational principles that underlie this behavior? And then now, the goal is go into the brain and see, is there a correlate of that? Is there evidence that neurons and sort of biology is actually implementing those types of algorithms?


Kiara: And you mentioned initially that your lab was thinking about moving into more invasive methods. Right? What would be your ideal experiment using these more invasive methods and what type of invasive methods are you actually thinking about?

Dr. Yau: Right. So, with my training in graduate school, we were doing awake recordings in non-human primates and macaque, monkeys, right? So, we would drive micro electrodes into somatosensory cortex and then record extracellular voltage changes. And it's a basically we are in the process of resuming that type of work. And the idea would be, you know, getting down to neurons, individual neurons, or recording activity from groups of neurons. And so now we can look at multi-unit activity, look at local field potentials. And you know, try to again relate, the activity patterns to the sensory information that we're providing, right, to the skin or try to relate the activity patterns that we are measuring to the behavioral reports that the observer in this case, you know, it could be human observer or an animal observer, could be reporting at that and try to look at again. How does that activity relate to their behavior? Their perception? Right?

Kiara: Hmm. Ideally, would you be able to perform these experiments on humans or…?

Dr. Yau: Right. So, we are ready with the non-invasive method were sort of developed with the behavioral paradigms. We're developing some intuition for where the brain is, could occur the computations, even predicting fMRI signals, right? We have come up with encoding models that allow us to do that. We're, in addition to these non-invasive approaches, where started collaborations with neurosurgeons here at Baylor, or with neurosurgeons and other institutions, including at Hopkins, where now we can potentially record, invasive activity or record activity, invasively in human volunteers, and then we can again start to ask questions related to local field potential recordings from ECog in humans or even you know, invasive penetrating, electrodes in human volunteers. What is the electrical activity that we're measuring? How does that relate to stuff that they're feeling on their hands?

Kiara: That's great. So those are all the questions that I have for you. I've learned a lot. Thank you so much.

Erik: Same. Same.

Kiara: Yeah. Thank you so much for doing this. It's been a pleasure. I don't know.

Erik: Yeah, you know. We appreciate your time. Yeah, and sorry we couldn't do this in person. But you know…

Dr. Yau:  Sure!

Kiara: I think this setup worked out actually pretty fine. Yeah.

Dr. Yau: Okay, great. Well, this is great. I enjoyed this very much and if you want to talk more, I mean, clearly, I'm happy to talk, right? So, I think that, you know, if there's anything that you want to follow up on, I'm happy to talk some more.

Kiara: Definitely. This has brought up a lot of questions that I hadn't even thought of before about multi-sensory processing. So, thank you so much.

Erik: Yeah, thank you.

Dr. Yau: Okay. All right. Take care!

Kiara: You too. Have a good night.

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